A Randomized Clinical Trial Comparing 4-Port, 3-Port, and Single-Incision Laparoscopic Cholecystectomy

Journal of Investigative Surgery, Early Online, 1 8, 2013 Copyright C 2013 Informa Healthcare USA, Inc. ISSN: 0894-1939 print / 1521-0553 online DOI: 10.3109/08941939.2013.856497 ARTICLE A Randomized Clinical Trial Comparing 4-Port, 3-Port, and Single-Incision Laparoscopic Cholecystectomy Zhamak Khorgami, MD, 1,2 Saeed Shoar, MD, 1 Taha Anbara, MD, 1 Ahmadreza Soroush, MD, 1,2 Shirzad Nasiri, MD, 1,2 Ali Movafegh, MD, 3 Ali Aminian, MD 4 1 Department of surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 2 Research Center for Improvement of Surgical Outcomes and Procedures, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 3 Department of Anesthesiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, 4 Department of surgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran ABSTRACT Backgrounds: Despite increasing trend in single incision laparoscopic cholecystectomy (SILC), there is still controversy regarding its global acceptance as a routine practice. Our study aimed to compare surgical events, early in-hospital and later outcomes of SILC with conventional multiport laparoscopic cholecystectomy (LC). Methods: Through a randomized controlled trial (RCT) between June and December 2011, 90 consecutive patients with documented biliary diseases waiting for LC were equally allocated to 3-port, 4-port, and single incision LC group. Operative time, surgical adverse events, postoperative pain according to visual analogue scale (VAS), total morphine administration, length of hospital stay, and cosmetic outcomes were compared between these three groups. Results: A total of 27 males (30%) and 63 females (70%) were enrolled in this study. The average patients age and BMI were 42.6 ± 12.1 years and 26.2 ± 2.7 kg/m 2, respectively. Operative time in SILC group was significantly longer than other groups. Total intraoperative adverse events and postoperative complications did not differ significantly between the three groups. Mean ± SD VAS score at rest was significantly lower (p < 0.05) in SILC group. The average VAS at coughing was significantly lower in SILC group in all time intervals except the first 6 hr (p < 0.05). In addition, total morphine dose showed significantly lower amount in SILC group (p = 0.02). 12-month follow-updid not reveal significant difference between the study groups (p > 0.05). Conclusion: SILC is associated with less postoperative pain in later hours, reduces in-hospital analgesic dosages, has longer procedure time, but does not increase intraoperative and postoperative adverse events It seems that SILC has no obvious advantages in terms of later outcomes. Keywords: single incision laparoscopic surgery; single incision laparoscopic cholecystectomy; outcomes INTRODUCTION Surgery is the most common treatment for benign diseases of the gallbladder (GB) [1], and such techniques have evolved over the past few decades [2]. Currently, laparoscopic cholecystectomy (LC) is considered the gold standard surgical treatment for biliary stone-related diseases of the GB [2 4]. Surgeons have started developing less invasive surgical techniques to further enhance the benefits of LC [4, 5]. Therefore, single-incision LC (SILC) has received much attention since it was first reported in 1997 [5], and many authors have reported their experience with SILC to date [6 11]. Several studies have discussed the adverse events of SILC in terms of pain scores and wound complications [12, 13], while numerous other studies have documented the safety and feasibility of SILC [14 19] and highlighted the potential advantages of decreased incisional pain [20]. A multicenter randomized controlled trial (RCT) showed that SILC should be considered as an alternative only for patients for whom increased cosmesis is more important than avoiding the more severe postoperative pain and possibly higher rate of wound complications related with this procedure [13]. Despite a growing body of evidence, few highpowered trials have compared the postoperative Received 6 April 2013; accepted 14 October 2013. Address correspondence to Zhamak Khorgami, MD, Department of Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Email: khorgami@tums.ac.ir 1

2 Z. Khorgami et al. complications, patients objective pain assessment, and cosmetic outcomes for SILC with those for conventional multiport LC [21]. This paucity of knowledge is quite detrimental as the longer operation time, a higher possibility of surgical adverse events, and wound complications related with SILC weigh against its potential benefits. Hence, we conducted this prospective RCT to compare intraoperative adverse events as well as early in-hospital and later outcomes for the three different surgical approaches of LC: the use of four ports, three ports, and a single incision. PATIENTS AND METHODS Study Design and Subjects This double-blind RCT was conducted at Shariati Hospital, a teaching hospital affiliated with Tehran University of Medical Sciences, between June and December 2011. Patients who were older than 18 years and had a documented indication for LC on the basis of clinical and radiologic findings were included in this prospective study. Exclusion criteria included the suspicion of complicated cholecystitis, body mass index (BMI) 35 kg/m 2, drug addiction, American Society of Anesthesiologist (ASA) physical classification > 2, previous surgery in the upper abdomen, and pregnancy. To estimate the study power, total administered morphine was used as primary endpoint considering a 20% reduction in total morphine dosage clinically relevant. Assuming the first type error as α = 0.05 and deeming a power of 80%, a total sample size of 75 patients (25 subjects per group) was calculated adequately. The research ethics committee of the university approved the study protocol. Informed consent was obtained from each patient. A total of 90 consecutive patients were equally randomized to the 4-port LC (4PLC), 3-port LC (3PLC), and SILC groups by using a central randomization process based on a computergenerated list coordinated by an independent statistician who was not otherwise involved in the study. In all groups, four dressings were placed over the usual sites for 4PLC to blind both the patients and nurses responsible for the pain score evaluation and the data gathering to the type of procedure used until the postoperative visit during the first week. However, it was not possible to blind the surgeons to the type of procedure. Surgical Procedure General anesthesia was induced and maintained using a standardized protocol. General anesthesia was induced with propofol (2 mg/kg) and sufentanil (0.3 μg/kg). Tracheal intubation facilitated by injection of Atracurium (0.5 mg/kg). Anesthesia during surgery was maintained with isoflurane 1.2% and administration of Atracurium (0.1 mg/kg) and sufentanil (0.1 μg/kg) every 30 min. The patients were monitored by ECG, pulse oximetry, noninvasive blood pressure, and capnography. Patients were recovered by administration of neostigmine (40 μg/kg) and atropine (15 μg/kg). Fluid therapy protocol in terms of volume and kind of Crystalloid injection was similar in three groups. Under sterile conditions, the umbilicus was cautiously cleaned and the abdominal surface was prepared and draped for surgery. The patient was positioned supine, in approximately 30 reverse Trendelenburg position. SILC Using conventional instruments and equipment, a 2.5- cm vertical incision was made inside the umbilicus. After insertion of a Veress needle, CO 2 pneumoperitoneum was created and preserved at a pressure of 14 mmhg. A 10-mm port was used in the most inferior portion of the incision and two 5-mm ports were used in the upper left and right corners through the medial portion of rectus sheets (Figure 1). We started the procedure with insertion of a 0 10- mm camera through the 10-mm port and changed it to a 30 camera when required. Conventional rigid instruments were used throughout the operation. Cholecystectomy procedure was performed using the same rules of classic LC. Using the grasper via the right upper port, GB was grasped at the infundibulum initially and retracted to the upper and right side. A Maryland dissector was inserted via the left upper port to dissect the Calot s triangle and determine critical view of safety. During the dissection, only grasper was used for infundibular retraction and no other mean was utilized for retracting GB. We used 5-mm Hem-o-lok clips (Weck, Research Triangle Park, NC, USA) to ligate cystic artery and duct. To retrieve the GB, we used a handmade endo-bag composed of a surgical glove with purse-string suturing at the opening continuing as a long thread to drag out the bag through the 10-mm port. When the GB was completely separated, we temporarily removed the camera and entered the bag from 10-mm port with the distal part of connected thread (tail of purse string in the opening of the bag) still outside. Using the connected thread, we took out the bag containing GB by pulling the bag to the 10-mm opening. At the end of the procedure, the 10-mm port site was closed using 1.0 Vicryl for the fascia. Having performed more than 25 SILC procedures prior to this study, our surgeons (Zhamak Khorgami, Shirzad Nasiri, and Ahmadreza Soroush) were already proficient with this technique passing its learning curve [22]. Journal of Investigative Surgery

Outcomes of Single Incision Laparoscopic Cholecystectomy 3 4PLC FIGURE 1. Umbilicus with three inserted ports in SILC. Standard 4PLC was performed using a 10-mm trocar in the umbilicus accompanied by three 5-mm trocars placed in the epigastric, middle right upper, or lower right lateral regions. 3PLC 3PLC procedure was performed by omitting the lower right lateral trocar described above. Postoperative Care Administration of the anesthetic agents was stopped after extubation; subsequently, the patients were closely observed in the postanesthetic care unit and then transferred to the surgical ward once their Aldrete score was 9. A bolus of morphine sulfate (0.1 mg/kg) was administered intravenously after the operation. In the postoperative period, patients received rescue doses of 1 mg morphine via a Patient-Controlled Analgesia Device (PCAD) (Accumate 1000; Wooyoung, SK) with an 8 min lock-out time. Patients were taught how to properly use the PCAD and the visual analogue scale (VAS) prior to the surgery. Discharge Criteria Based on our institution policy, patients who did not develop further complications were discharged the day after surgery if their VAS score was 4, oral feeding could be tolerated, and audible bowel sounds had returned. For this reason, outpatient surgery was not possible for our patients. C 2013 Informa Healthcare USA, Inc. Outcome Measures and Follow-up Data pertaining to surgical parameters such as operative time and undesirable intraoperative events, including significant bleeding at the surgical site (blood loss > 100 cc), GB perforation, and stone spillage, were recorded. Postoperative pain was evaluated using 10- cm VAS scores every 6 hr both at rest (VAS-rest) and during coughing (VAS-cough). Narcotic usage was also measured using the PCAD. At the first outpatient visit, 1 week after the surgery, patients were questioned about their need for analgesics to relieve their pain and about how long it took to return to work after discharge. During a 3- and 12-month telephone survey, they were asked to evaluate their overall satisfaction with the procedure and cosmetic results using a 10- point Likert scale and report it themselves. Statistical Analysis Data were analyzed using the Statistical Package for the Social Sciences (SPSS version 16; Chicago, Inc). Based on the Smirnov Kolmogorov test, operative time, VAS scores, total morphine dosage, time taken to return to work, and postoperative hospital stay were all compared among the 3 groups by using the nonparametric Kruskal Wallis test. Intraoperative and postoperative adverse events were compared among groups by using the chi square test. Although the data for nonparametric continuous/quantitative variables are usually presented in terms of median and interquartile percentage, we thought that the mean ± SD representation would be aid in comparison with the results of other studies. Hence, quantitative variables have been presented in terms of mean ± SD values,

4 Z. Khorgami et al. and the values have been considered statistically significant at p < 0.05. (p = 0.02). Hospital stay did not differ significantly among the three groups (p = 0.34). RESULTS A total of 90 patients, 27 males (30%) and 63 females (70%), were enrolled in this study and allocated equally to three groups of SILC, 3PLC, and 4PLC. The average patients age and BMI were 42.6 ± 12.1 years and 26.2 ± 2.7 kg/m 2, respectively. The three groups did not significantly differ with respect to age, gender, BMI, or indication for surgery (p > 0.05). Most of the patients (57.8%) underwent the LC for biliary colic (Table 1). Operative Time and Intraoperative Adverse Events One patient in the 3PLC group and three patients in the SILC group were converted to conventional 4PLC in order to ensure the required critical view of safety during the surgery. However, their data was considered in their initial group and analyzed accordingly. The operative time for the SILC group (63.7 ± 9.8 min) was significantly longer (p = 0.007) than that for the 3PLC (54.2 ± 14.4 min) and 4PLC (53 ± 13.5 min) groups. Intraoperative adverse events occurred in five patients in the SILC group (16.7%), five patients in the 3PLC group (16.7%), and four patients in the 4PLC group (13.3%), but the differences were not significant (p = 0.84). Postoperative complications and complaints did not differ significantly among the three groups (eight patients (26.7%) in the 4PLC group, 10 patients (33.3%) in the 3PLC group, and five patients (16.7%) in the SILC group; p = 0.7). Table 2 presents the intraoperative and postoperative events in detail. Postoperative Pain The mean ± SD VAS score at rest was significantly lower (p = 0.02) in the patients of the SILC group (1.7 ± 0.8) than in the patients of the 3PLC (2 ± 1.2) and 4PLC (2.5 ± 1.2) groups. With respect to the VAS during coughing, the average pain score at all time intervals except for the first 6 hr was significantly lower in the SILC group (p < 0.05), as detailed in Table 3. The first VAS score at the time of coughing was lower in the SILC group, although the difference was not significant (6.2 ± 1.7 in the SILC group, 6.6 ± 1.6 in the 3PLC group, and 6.3 ± 2.1 in the 4PLC group; p > 0.05). In addition, total morphine administration by PCAD showed a mean ± SD value of 4.7 ± 3.4 ml in the SILC group, 6.9 ± 3.7 ml in the 4PLC group, and 7.2 ± 3.6 ml in the 3PLC group; the value for the SILC group was significantly lower than those for the other groups Follow-up There were no readmission, reoperation, and mortality in this cohort of patients. In terms of patients selfevaluated outcomes either in 3-month or 12-month follow-ups, no statistically significant difference was observed in cosmesis, the average number of days taken to return to work, need to take analgesics after discharge, and overall satisfaction among the three groups (p > 0.05). Data regarding patients late outcomes are summarized in Table 4. DISCUSSION SILS has received much attention over the past few years [10, 21, 23]; it generally starts with cholecystectomy and is performed using a 1-wound laparoscopic surgical procedure or by using specific ports [24 27]. SILS has been under study in other subspecialty fields of surgery, including bariatric surgery [28], colorectal disease [29, 30], and for other procedures performed in the abdominopelvic cavity [31, 32]. However, wide spread of this novel technique requires further evaluation of its potential risks and benefits, cost effectiveness, and long-term clinical, surgical, and cosmetic outcomes. In our study, SILC could be safely performed in 27 of 30 patients; however, the procedures were converted to 4PLC in three patients. One case of conversion occurred in the 3PLC group as well. This conversion rate is slightly higher than that reported in the RCT performed by Phillips et al. in which only one patient required conversion to 4PLC [13]. This difference may arise from the fact that our operations were performed using traditional instruments. The difference may also occur due to the level of surgeon s threshold in critical view for changing to a safer approach. Intraoperative adverse events were similar among three groups in our study, and no significant differences were seen with respect to GB perforation, bleeding in the GB bed, stone spillage, or clip separation (accidental separation of clip on the GB; after cutting the cystic duct). The incidence of postoperative complications, including surgical wound infection, nausea/vomiting, and the need for antiemetic drugs, did not differ among groups. However, there was only one case of port-site hernia in 3-port group which needed surgical correction. In contrast, Phillips et al. showed that the SILC group had more frequent surgical site complications than the 4PLC group (10% vs. 3%) because of local ischemia due to higher pressure of a larger single port [13]. However, our technique involves the insertion of usual Journal of Investigative Surgery

Outcomes of Single Incision Laparoscopic Cholecystectomy 5 TABLE 1. Patients demographics and primary clinical characteristics 4PLC (n = 30) 3PLC (n = 30) SILC (n = 30) p value Age (years) 41.5 ± 11.1 41.7 ± 11.2 43.81 ± 12.7 0.40 Sex (n) 0.80 Male 9 (30%) 10 (33.3%) 8 (26.7%) Female 21 (70%) 20 (66.7%) 22 (73.3%) BMI (kg/m 2 ) 26.7 ± 4 28.6 ± 4.5 27.9 ± 4.3 0.60 Indication for Surgery 0.85 Biliary colic 19 (63.3%) 16 (53.3%) 17 (55.6%) Cholecystitis 6 (20%) 8 (26.7%) 8 (26.7%) Biliary pancreatitis 3 (10%) 4 (13.3%) 2 (56.7%) CBD stone removed by ERCP 2 (6.7%) 2 (6.7%) 3 (10%) TABLE 2. Surgical adverse events 4PLC (n = 30) 3PLC (n = 30) SILC (n = 30) p value Operative time (min) 53 ± 13.5 54.2 ± 14.4 63.7 ± 9.8 0.007 Total intraoperative Events 4 (13.3%) 5 (16.7%) 5 (16.7%) 0.84 Gallbladder perforation 3 (10%) 3 (10%) 2 (6.7%) 0.90 Bleeding in GB bed 1 (3.3%) 1 (3.3%) 1 (3.3%) 0.85 Stone spillage 0 (0%) 0 (0%) 0 (0%) N/A Clip separation 0 (0%) 1 (3.3%) 2 (6.7%) 0.43 Total postoperative complaints 8 (26.7%) 9 (30%) 5 (16.7%) 0.50 Nausea/vomiting 8 (26.7%) 9 (30%) 5 (16.7%) 0.55 Need to antiemesis 4 (13.3%) 6 (20%) 2 (6.7%) 0.35 Total postoperative complications 0 (0%) 1 (3.3%) 0 (0%) N/A Wound infection/dehiscence 0 (0%) 0 (0%) 0 (0%) N/A Port-site hernia 0 (0%) 1 (3.3%) 0 (0%) N/A N/A: Not applicable. TABLE 3. Patients early in-hospital outcomes (mean ± SD) 4PLC 3PLC SILC p value VAS-rest a 6 hr 5.4 ± 1.7 5.0 ± 1.4 4.7 ± 1.5 0.14 12 hr 4.6 ± 1.6 4.2 ± 1.2 3.7 ± 1.2 0.07 18 hr 3 ± 1.6 3.3 ± 1.2 2.5 ± 1.3 0.45 24 hr 2.5 ± 1.2 2.1 ± 1.2 1.6 ± 0.7 0.03 VAS-cough a 6 hr 6.3 ± 2.1 6.6 ± 1.6 6.2 ± 1.7 0.39 12 hr 5.9 ± 1.8 5.6 ± 1.4 5.1 ± 1.4 0.04 18 hr 4.4 ± 1.6 4.8 ± 1.1 3.6 ± 1.3 0.03 24 hr 3.9 ± 1.5 3.7 ± 1.3 2.4 ± 1.2 <0.0001 Total morphine (mg) 6.9 ± 3.7 7.2 ± 3.6 4.7 ± 3.4 0.02 Postoperative hospital stay (days) 1.2 ± 0.4 1.1 ± 0.4 1 ± 0.2 0.23 a Reported as mean ± SD score. TABLE 4. Patients self-reported long-term outcomes 4PLC (n = 30) 3PLC (n = 30) SILC (n = 30) p value Return to work (days) 5.8 ± 2.5 6.4 ± 3.7 7.2 ± 3.5 0.80 Analgesic intake b 6 (20%) 6 (20%) 3 (10%) 0.53 Cosmesis self-assessment a 3 months 9.7 ± 0.5 9.5 ± 0.6 9.9 ± 0.3 0.23 12 months 9.8 ± 0.4 9.4 ± 0.7 9.7 ± 0.5 0.21 Satisfaction score a 3 months 9.2 ± 0.7 8.9 ± 0.8 9.3 ± 0.7 0.16 12 months 9.1 ± 0.5 9± 0.6 9.2 ± 0.4 0.18 a Reported as mean ± SD score based on a 10-point Likert scale (NRS). b Number of patients taking analgesic after discharge. C 2013 Informa Healthcare USA, Inc.

6 Z. Khorgami et al. ports (10 and 5 mm) rather than a larger multiport instrument that is commonly used in SILS; therefore, it avoids the development of a large fascial wound that bears an increased risk of wound complications. There was no major complication in this study. On the other hand, Joseph et al. indicated that bile duct injury, with an SILC-associated injury rate of 0.72%, is more common in SILC than in conventional LC. Moreover, they noted that this rate is regardless of complicated circumstance such as inflammation at the site of surgery because at this time most of SILS are done in optimal conditions [7]. The operation time was reasonable in all surgeries in the present study; as a rule, it tends to decrease as the surgeon s experience increases. However, the surgeries lasted significantly longer in the SILC group (63 min) than in the other multiport procedures (53 min). Also in study of Phillips et al., an average operative time of 57 min versus 45 min in SILC and multiport groups has been reported [13]. Other evidence also supports the finding of a longer operative time for SILC than for multiport LC [21]. However, data heterogeneity and statistical bias are still observed. The VAS-rest at 24 hr and VAS-cough scores from 12 to 24 hr on the first postoperative day were significantly lower in the SILC group. In addition, total morphine use was significantly lower in SILC group, followed by the 4PLC group and then the 3PLC group. In comparison, other studies have reported varying results. While some have considered SILC to be associated with increased surgical wound pain on the first postoperative day [13], some other studies have reported no significant difference in VAS scores between SILC and standard multiport LC on the day of surgery [21]. Not all of these studies have discussed the amount of analgesic administered or the objective assessment of postoperative pain. Of these, the one performed by Phillips et al. showed no significant difference in analgesia use [13]. This difference in results between our study and other studies may have arisen from the differing method of port insertion, as we inserted three trocars at three different fascia holes rather than specialized large SILS ports which makes larger fascial opening with possible more pain and subsequent port-site hernia. However, this concept is not proven and needs further studies. We also objectively evaluated patients pain by using PCAD. The postoperative hospital stay duration was similar among our groups which is in the same line with other studies [21]. Similarity of length of hospital stay could be the result of the minimal surgical complications and faster recovery in relation to LC and its minimal invasiveness. The patients self-evaluation of the cosmetic results, time taken to return to work, need to taking analgesics after discharge, and overall satisfaction did not differ among the SILC and multiport groups. In a systematic review, Sajid et al. analyzed a pooled data from 11 RCTs encompassing 858 patients [8]. Their meta-analysis showed that there was no statistically difference between the SILC group and the conventional LC group in terms of postoperative complication rate, length of hospital stay, cosmesis score, conversion rate, and time taken to return to work. Furthermore, their subgroup analysis showed no statistical difference between groups in terms of postoperative pain [8]. Although, our study did not show any significant difference in intraoperative events, postoperative complications, and 12-month outcomes but further studies with larger sample size, may reveal small differences. Incision length is an important determinant of postoperative pain [8]. However, there is no reported difference between the number of ports and perioperative pain score. This effect is obviously seen in our study since there was no association between the study endpoints and the number of ports in the 3PLC and 4PLC groups. In fact, since the pain scores in SILC group were lower than 3PLC and 4PLC groups, we can conclude that lower pain scores in SILS is probably due to accumulating the three ports in a single entry site in the umbilicus and not because of decreasing the number of ports. Changing the upper ports to a lower position in the umbilicus might lead to lower pain scores in SILC because the epigastric and right upper quadrant ports are prone to more pain due to respiratory movements. The use of different numbers of ports should be taken into account when evaluating the total cost of laparoscopic procedures. In this study, we used the classic surgical glove to construct a handmade bag to grasp the excised GB and avoid the need to use the jelly port system that has been recently widely used in LCs because of its higher costs and its unavailability in our region. Finally, the impact of different operation times, surgical incision lengths, hospital stays, analgesia intake, and time away from work on the costeffectiveness of SILC versus conventional techniques should be considered. With this in mind, advantages of SILC may not justify its more demanding techniques as we observed longer operation time with no benefit in regard to other variables. The most significant benefit of SILS over 4PLC and 3PLC will be in the postoperative period with less pain and analgesic use. However, this may be affected by different ports insertion techniques and needs further studies to determine the best methods of SILS. Using the best SILS technique with the least postoperative pain can be a way to more efficient fast-track surgery, shorter hospital stay, and less hospital costs in minimally invasive surgery. However, because SILS is technically more demanding and has questionable long-term advantages [8] and there are concerns about higher rate of biliary tract injury [7], surgeons should have a low threshold to convert SILS to conventional laparoscopic surgery. Our study had some limitations that should be noted before its findings are interpreted. One limitation is Journal of Investigative Surgery

Outcomes of Single Incision Laparoscopic Cholecystectomy 7 that we used conventional instruments for SILS which differs from routinely practiced methods in the world. Further high-power RCTs that use larger sample sizes and a special single port should be performed to determine the ideal surgical technique for performing SILC. These studies should also measure the costs associated with SILC and weigh them against its benefits and even consider the components of quality of life. The other limitation of our study was our institution policy that all patients should stay the night and will be evaluated the day after surgery for discharge criteria (due to metropolitan nature of the city and lacking of widespread home care). Therefore, it is hard to judge about hospital stay as an outcome in this study. This limitation should also be noticed in future studies to give a pragmatic estimate of patients outcomes. In conclusion, SILC results in decreased postoperative pain in later postoperative hours and reduces inhospital analgesic dosages compared to those for conventional methods. Omitting upper abdominal incisions may result in decreased respiration-related pain. SILC is not associated with increased intraoperative and postoperative adverse events but has increased procedure time even when performed in selected patients. However, SILC appears to have no obvious advantages in 12-month outcomes. ACKNOWLEDGMENT We extend our thanks to Dr. Delaram Shakoor and Dr. Shirin Mahdavian for their warm help during this study. Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. REFERENCES 1. Keus F, de Jong JA, Gooszen HG, et al. Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database Syst Rev. 2006;4:CD006231. 2. de la Fuente SG, Demaria EJ, Reynolds JD, et al. New developments in surgery: natural orifice transluminal endoscopic surgery (NOTES). Arch Surg. 2007;142(3):295 297. 3. Slim K, Pezet D, Stencl J, et al. Laparoscopic cholecystectomy: an original three-trocar technique. World J Surg. 1995;19(3):394 397. 4. Kaiser AM, Corman ML. History of laparoscopy. Surg Oncol Clin N Am. 2001;10(3):483 492. 5. Navarra G, Pozza E, Occhionorelli S, et al. One-wound laparoscopic cholecystectomy. Br J Surg. 1997;84(5):695. 6. Song S, Itawi EA, Saber AA. Natural orifice translumenal endoscopic surgery (NOTES). J Invest Surg. 2009;22(3):214 217. 7. Joseph M, Phillips MR, Farrell TM, et al. Single incision laparoscopic cholecystectomy is associated with a higher bile duct injury rate: a review and a word of caution. Ann Surg. 2012;256(1):1 6. 8. Sajid MS, Ladwa N, Kalra L, et al. Single-incision laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy: meta-analysis and systematic review of randomized controlled trials. World J Surg. 2012;36(11):2644 2653. 9. Garg P, Thakur JD, Garg M, et al. Single-incision laparoscopic cholecystectomy vs. conventional laparoscopic cholecystectomy: a meta-analysis of randomized controlled trials. J Gastrointest Surg. 2012;16(8):1618 1628. 10. Hall TC, Dennison AR, Bilku DK, et al. Single-incision laparoscopic cholecystectomy: a systematic review. Arch Surg. 2012;147(7):657 666. 11. Song T, Liao B, Liu J, et al. Single-incision versus conventional laparoscopic cholecystectomy: a systematic review of available data. Surg Laparosc Endosc Percutan Tech. 2012;22(4):e190 e196. 12. Luo C, Yang Q, Liu B, et al. Difficulties and countermeasures of transumbilical single incision laparoscopic cholecystectomy. J Am Coll Surg. 2012;214(5):e35 e38. 13. Phillips MS, Marks JM, Roberts K, et al. Intermediate results of a prospective randomized controlled trial of traditional four-port laparoscopic cholecystectomy versus single-incision laparoscopic cholecystectomy. Surg Endosc. 2012;26(5):1296 1303. 14. Karim MA, Ahmed J, Mansour M, et al. Single incision vs. conventional multiport laparoscopic cholecystectomy: a comparison of two approaches. Int J Surg. 2012;10(7):368 372. 15. Abdelaziz Hassan AM, Elsebae MM, Nasr MM, et al. Single institution experience of single incision trans-umbilical laparoscopic cholecystectomy using conventional laparoscopic instruments. Int J Surg. 2012;10(9):514 7. 16. Choi SH, Hwang HK, Kang CM, et al. Single-fulcrum laparoscopic cholecystectomy: a single-incision and multiport technique. ANZ J Surg. 2012;82(7 8):529 534. 17. El-Geidie AA. single-incision laparoscopic cholecystectomy (SILC) using harmonic scalpel. J Surg Res, 2012; 176(1):50 54. 18. Cui H, Kelly JJ, Litwin DE. Single-incision laparoscopic cholecystectomy using a modified dome-down approach with conventional laparoscopic instruments. Surg Endosc. 2012;26(4):1153 1159. 19. Sumiyoshi K, Sato N, Akagawa S, et al. Single-incision laparoscopic cholecystectomy with needle graspers. Hepatogastroenterology. 2012;59(114):325 328. 20. Beck C, Eakin J, Dettorre R, et al. Analysis of perioperative factors and cost comparison of single-incision and traditional multi-incision laparoscopic cholecystectomy. Surg Endosc. 2013;27(1):104 8. 21. Markar SR, Karthikesalingam A, Thrumurthy S, et al. Single-incision laparoscopic surgery (SILS) vs. conventional multiport cholecystectomy: systematic review and meta-analysis. Surg Endosc. 2012;26(5):1205 1213. 22. Qiu Z, Sun J, Pu Y, et al. Learning curve of transumbilical single incision laparoscopic cholecystectomy (SILS): a preliminary study of 80 selected patients with benign gallbladder diseases. World J Surg. 2011;35(9): 2092 2101. 23. Markar S, Kinross J. Authors reply to: single-incision laparoscopic surgery (SILS) vs. conventional multiport cholecystectomy: systematic review and meta-analysis. Surg Endosc. 2012;26(10): 3000 3001. 24. Yeo D, Mackay S, Martin D. Single-incision laparoscopic cholecystectomy with routine intraoperative cholangiography and common bile duct exploration via the umbilical port. Surg Endosc. 2012;26(4):1122 1127. 25. Joseph M, Phillips M, Rupp CC. Single-incision laparoscopic cholecystectomy: a combined analysis of resident and attending learning curves at a single institution. Am Surg. 2012;78(1):119 124. C 2013 Informa Healthcare USA, Inc.

8 Z. Khorgami et al. 26. Sasaki K, Watanabe G, Matsuda M, et al. Single-incision laparoscopic cholecystectomy: comparison analysis of feasibility and safety. Surg Laparosc Endosc Percutan Tech. 2012;22(2):108 113. 27. Arroyo JP, Martin-Del-Campo LA, Torres-Villalobos G. Single-incision laparoscopic cholecystectomy: is it a plausible alternative to the traditional four-port laparoscopic approach? Minim Invasive Surg. 2012;2012: 347607. 28. Chakravartty S, Murgatroyd B, Ashton D, et al. Single and Multiple Incision Laparoscopic Adjustable Gastric Banding: a matched comparison. Obes Surg. 2012; 22(11):1695 700. 29. Paranjape C, Ojo OJ, Carne D, et al. Single-incision laparoscopic total colectomy. JSLS. 2012;16(1):27 32. 30. Makino T, Milsom JW, Lee SW. Single-incision laparoscopic surgeries for colorectal diseases: early experiences of a novel surgical method. Minim Invasive Surg. 2012; 2012:783074. 31. Yang G, Lai E, Chan O, Tang C, et al. Single-incision transabdominal preperitoneal and totally extraperitoneal repair for inguinal hernia: early experience from a single center in Asia. Asian J Endosc Surg. 2011;4(4):166 70. 32. Iida T, Kawa G, Takizawa N, et al. Laparoendoscopic single-site surgery for urachal remnants. Asian J Endosc Surg. 2012;5(2):100 102. Journal of Investigative Surgery